The Connection Between Cleanliness, Our Immune System, and Allergies

To blame increased sanitation would be an oversimplification… The immune system’s work balance has been changing too! The shocking truth.

    The skin is the most visible part of us, covering our entire body. It’s easy to take it for granted and forget to be grateful for it but it’s the body’s largest and strongest organ. Also, it doesn’t just separate us from the outside world, it is also a sense organ, letting us feel if something is hot or cold, painful or itchy.

The most common ailment that affects our skin is atopic dermatitis. It is an ailment that shows as an allergic reaction. Patients presenting with allergic reactions have been steadily increasing in the past decade or so in Japan but the ‘hygiene theory’ claims that it is due to the fact that out living environments have become too hygienic. We are going to look into the relation between allergies, focusing on atopic dermatitis, and our sanitation.

*The contents of this article has been reworded from “The Wonder of the Skin, the Human Body’s Largest Organ, it’s all-round utility that science has recently discovered” (Jintai Saikyou no Zouki Hifu no Fushigi – Saikin Kagaku de wakatta Bannousei)

Why have allergy patients suddenly increased in the past 40-50 years?

    Humans suffer from a wide range of illnesses. Infections such as smallpox or influenza, incurable cancers and lifestyle diseases like diabetes and high blood pressure. But above all, the illness that has skyrocketed in recent times are allergic reactions.

An allergic reaction is when the body’s immune system overreacts to a specific antigen. These reactions occur towards things that are in themselves harmful to the body, like dust, pollen or cat fur. The immune system then overreacts to these things and causes blocked and/or runny noses, sneezing, rashes and itchiness or breathing complications. Aside from anaphylactic shock and serious asthma, allergies aren’t life-threatening conditions but once they appear, they can cause a marked decline in quality of life.

Hay fever is a type of allergy that is cause by the pollen of plants like the cedar or cypress tree and can cause sneezing, runny nose and itchy eyes. The first reported case of hay fever was in 1961 (Japan?) but the cases have grown streadily over the years and today about 1 in 3 people in Japan suffer from hay fever.

Other than that, there are various other varieties such as food allergies, allergic rhinitis, allergic conjunctivitis, bronchial asthma. In actuality about 1 in every 2 people in Japan has one type of allergy, causing allergies to be named a national disease.

The causes of allergic reactions are called allergens and these allergens exist abundantly in the world around us. Its not just dust, or cedar and cypress pollen but also many foods we are familiar with such as eggs, milk, flour, peanuts, prawn/shrimp and crab aswell as the corpses of mites.

It differs from individual to individual, but once an allergen enters the body, they are deemed a foreign substance and the bodies immune system moves to destroy it and creates a substance called Antigen IgE.

Then, if an allergen re enters the body, the allergen is caught by the IgE allergen on the surface of a mastocyte cell that store histamines and other chemicals. These histamines are chemical messengers are then released in mass and cause the symptoms of an allergic reaction.

The immune system is a defence system that protects our bodies against foreign infectious bodies such as viruses, bacteria and parasites. The mechanism reacts to substances and food that do not in themselves cause the body harm so why the excessive immune response? And why it is that allergy cases have been increasing so much up until now?

Asides allergies, lots of illnesses and diseases occur as a result of the combination of genetics and an individual’s environment. Just 40 to 50 years ago, It is hard to think that human genes would have mutated to a type that would make us susceptible to allergies in just the last 40-50 years and the main reason for this sudden increase is thought to be changes to our lifestyle choices and/or environment.

Today the prevailing theory is hygiene

    Nowadays, the prevailing theory is that it is the ‘Hygiene Theory’. This theory says that due to the huge improvement in our hygiene practices in recent years, there are few bacteria, viruses or parasites in our immediate vicinity and we have come to live in ‘too clean’ environments. As such, our immune system doesn’t get trained as it would have before and so it is easier for overreactions to specific allergens to occur.

The ’Hygeine Theory’ was first proposed by David Strachan of London University, UK. Strachan studied the occurrences of allergies in around 17,000 British people up until they turned 23 in his thesis published in the British Medical Journal in 1989. Strachan noticed that individuals who did not have siblings had a higher rate of allergy.

He then suggests that children with no siblings had less exposure/infection from bacteria/viruses/parasites during their upbringing causing their immune systems to be weaker and making allergic reactions more probable.

Furthermore, Strachan proposes that due to the increase in household cleaning/hygiene goods and a heightened awareness of cleanliness, exposure to infection in the home has decreased. The common knowledge up until that point was that the increase of hygienic goods and the decrease in exposure to pathogens was good for our health, so the ‘hygiene theory’ certainly was a wake-up call. It wasn’t a surprise that this research came from Britain, famous for its advanced public health.

Following this, theses regarding the hygiene of the environment that children are brought up in were published one after the other.

For example, reports from the USA explained how Amish children who were brought up on a farm with livestock had significantly less IgE antibodies with lower rates of allergy than children who were born in the same area but not on a farm. Also, if a child was born into a family who owned 2 or more pets, such as cats or dogs, before the child was 1 year old, they too were found to have less occurrences of allergies later in life.

Allergy cases are certainly continuing to increase rapidly in developed countries where sanitation is higher. Developing countries were sanitation isn’t sufficiently developed are not seeing the same increase. Also, if we look back on the path us Japanese have taken, ever since the high-growth period of the 1960s when roundworms, fleas and lice were mostly eradicated, our immune system which was built to eliminate such parasites has become redundant.

An insufficiently trained immune system is much like an amateur soldier who has yet to experience war, now begins to attack harmless allergens like pollen and food causing the actualisation of allergies that did not exist before.

A hygienic environment can’t be the only thing to blame?

    It’s a clear and persuasive argument, but to attribute everything to a sanitary environment would be somewhat oversimplifying things. It isn’t just an increase in our cleanliness that is causing the increase in allergy cases.

For example, there are reports that say that if infants or young children are given too many antibiotics, it can cause changes to the helpful bacteria present in their gut which can make it easier for them to develop allergies. There are various opinions, but it is said that within our gut, there exists around 40 trillion bacteria weighing around 1-1.5kg that all contribute to immune response.

If you take antibiotics, these bacteria that coexist with us are removed and the carefully balanced and complex ecosystem is upset. As a result, the immune response in the gut becomes abnormal and results in allergic reactions, the theory says.

I don’t think that the theory that overly hygienic conditions could be causing allergies is incorrect, but there are surely other complicated factors contributing to this and to say that allergies do not occur if you live in a less than hygienic environment, or that this environment will prevent the onset of allergies is an inadequate theory. Whether or not the hygiene theory holds true or not, is still being debated today.

The mechanism behind the onset of allergies.

    Atopic dermatitis is a very typical allergy that presents on the skin. Accordingly, the mechanism that causes it’s onset too, is typical and shared by all those who suffer from it.

Here, we will explain the mechanism behind allergic reactions in simple terms, using hay fever as an example. (Picture: ‘How pollen causes allergies’).

- Pollen is broken down by the proteins contained withing mucous and then enters the mucous membrane in the eyes and nose.

- Dedritic cells absorb the components of the pollen and break them down.

- The dendritic cells, activate the helper T-cells by transmitting the composition information of the invading pollen.

- The activated helper T-cells release cytosine, a biologically active substance, which activates B cells, a variety of immune cell.

- These B cells, activated by helper T-cells, mass release a protein called IgE antibody.

- IgE antibodies attach to the surface of Mastocytes and await in preparation for the next pollen invasion.

- Pollen once more enters the body.

- The IgE antibodies on the surface of the mastocytes bind with the pollen proteins and then histamines are released from the mastocytes.

- The histamines cause an increase in production in mucous and the pollen is carried out of the body via mucous and tears.

Histamine also activates in blood vessels, making the mucous membranes to swell and causing your nose to block.
For an allergic reaction to occur, a specific antigen must be taken in and an overly sensitive reaction (steps 1-6 in the above picture) must occur.

The information of the allergen pollen is captured by the dendritic cells upon entering the epidermis via the eyes or nose. Next the dendritic cells pass on the pollen composition to the helper T-cells and to the B immune cells which produce antibodies. The IgE antibodies that the B cells produce bind to the pollen specifically and are released in mass. This IgE antibody binds to the surface of mastocytes and then waits for the pollen to re appear.

Once the first step of the immune response is established, the immune system can react rapidly from that point onwards.

Once the pollen enters the body again, the mastocytes, already equipped with the specific IgE antibodies, bind to them. When this happens, the histamines within the mastocytes are released causing a runny nose, coughing and itchy eyes.

Mucous and coughing is a way to expel the pollen from the body, and our eyes itch to make us rub them, physically taking the pollen away with our hands. This is an extremely logical way of that our body quickly removes foreign objects.

The Two ‘Command Centers of the Immune System’

    The helper T-cells, introduced in the previous process are called the ‘immunity command center’ as they receiving antigen information and passing it on the the B cells that produce antibodies.

There are two varieties of these helper T-cells, the T helper 1 cell (Th1 cells) that causes the immune reaction that eliminates viruses, bacteria and the like, and the T helper 2 cell (Th2 cells) that causes the immune response that eliminates parasites. It is mostly the latter that is involved in an allergic reaction. Recently, inflammations caused by the latter are called type 2 inflammations.

These two types of T-cells actually both specialised from immature T-cells called Naïve T-cells so you could say that they are siblings in a way. The Th1 cells evolved from the naïve T-cells as a result of the interaction with the antigens expressed by the dendritic cells after having captured bacteria or a virus. The Th2 cells on the other hand, evolve from the interaction with the antigen produced when a dendritic cell captures a parasite.

The signalling molecules that Th1 and Th2 cells secrete are both different. (figure ‘The difference between Th1 and Th2 cells)

In Th1 cells, signalling molecules such as interferon gamma and IL-2 are secreted which activate killer T-cells, natural killer cells and B-cells which produce the IgG antibody which eliminates cells infected with viruses or bacteria.

The Th2 cells though, secrete signalling molecules such as IL-4, IL-5 and IL-13 and activate basophils and mastocytes, causing itchiness and sneezing and uses eosinophil, another type of white blood cell, to eliminate parasites.

A-1. Naïve T-cells, receive information from dendritic cells that have absorbed a virus/bacteria and transform into Th1 cells.

A-2. Th1 cells activate the IgG antibody producing B-cells and macrophages and then eliminate viruses and bacteria.

B-1. Naïve T cells receive information from dendritic cells that have absorbed a fragment of a parasite and become Th2 cells.

B-2. Th2 cells activate basophils and mastocytes.

In this way, the activation of Th2 cells is extremely important in the elimination of parasites but, as mentioned before, the increase in histamines released by the mastocytes upon binding to IgE becomes a cause of allergy.

The relationship between the 2 types of helper T-cell and a hygienic environment

    Th1 and Th2 cells govern each others functions depending on the environment they are in within the body and maintain a certain equilibrium (the Th1/Th2 balance). If this equilibrium tips in either direction, certain diseases could occur. It is thought that in those with allergies, the Th2 cells have become superior and so allergic reactions occur.

This theory is actually based upon the hygiene theory in that, due to one’s environment become too hygienic or sterile, the Th1/Th2 balance becomes upset and Th2 cells become superior.

It is generally said that if one’s environment is too sterile, it is easier for T-lymphocytes to specialise into Th2 cells and to cause allergic reactions, whereas, in an environment where pathogens such as bacteria are common, those T-lymphocytes specialise into Th1 cells, resulting in fewer allergies.

Translated by Ronnie Dickson

Source: 「清潔になって患者が増えた」は単純すぎ…それでも、免疫細胞の「仕事バランスは確実に変わっていた」という衝撃的な事実（現代ビジネス） - Yahoo!ニュース